The overall objective of this project is to study biochemical mechanisms involved in the metabolic activation of arylamines in non-hepatic target organs, with major emphasis on the urinary bladder. Recent studies from other laboratories have suggested a role for the N-glucuronide conjugates of the N-arylhydroxylamine metabolites in the induction of bladder cancer in susceptible species. The synthesis of a number of N-glucuronide conjugates will be undertaken for metabolic studies in appropriate host animals. If sufficiently stable, these N-glucuronides will be tested for carcinogenicity and for their ability to transform bladder epithelial cells in vitro. The project will also be concerned with determination of the potential role of N-sulfonate conjugates of N-arylhydroxylamines in bladder cancer induction. It is possible that N-glucuronides and N-sulfonates of N-arylhydroxylamines are involved in the induction of other cancers by arylamines in experimental animals.